Understanding Gene Therapy Delivery Challenges

Gene therapy delivery challenges are becoming more visible as more treatments reach FDA approval. In the last two years alone, roughly ten gene therapies have been cleared, signaling a major shift in how complex diseases are treated. In this episode of MedDevice by Design, Ariana Wilson and Mark Drlik explore what sits beneath that progress, focusing on how these therapies are delivered and why delivery remains one of the hardest problems to solve.

At their core, gene therapies are delivery mechanisms. Many rely on viral vectors, especially adeno-associated viruses, often called AAVs. These vectors act as carriers, transporting a genetic payload such as CRISPR to a target location where gene editing occurs. While this approach has enabled remarkable clinical advances, it also introduces serious technical and biological limitations.

AAVs, Immune Response, and Redosing Limits

One of the most pressing gene therapy delivery challenges involves the immune system. Because AAVs are viral, the body can develop an immune response after the first dose. This becomes especially problematic when redosing is required. A vector that successfully reached its target once may be blocked entirely during a second treatment.

As a result, many current therapies are designed as one-time treatments. This preference is shaping how new therapies are developed and how regulators evaluate them. However, it also places enormous pressure on the first dose to be precise, effective, and safe.

New Delivery Strategies and Targeted Dosing

To address these challenges, the industry is exploring several alternatives. These include engineered AAV capsids, non-viral delivery methods like lipid nanoparticles, and ex vivo or cell-based approaches. Each aims to reduce immune response while improving delivery accuracy.

Another major focus is lowering the effective dose. A single AAV treatment can contain 100 to 1,000 trillion viral particles, far more than the number of humans on Earth. All of those particles are attempting to reach the same target. By improving targeting and bypassing barriers like the blood brain barrier, developers can reduce unnecessary exposure and improve efficiency.

What This Means for the Future of Gene Therapy

As more therapies reach approval, delivery constraints will continue to shape innovation. Many current treatments focus on orphan diseases and non-heritable gene edits. Still, the momentum is clear. Regulatory precedent is growing, and interest in targeted, one-time therapies is accelerating.

This episode offers a practical look at how delivery decisions influence cost, safety, and long-term success. It also highlights why delivery is not just a technical detail, but a defining factor in the future of gene therapy.